This study aims to elucidate the pathways through which Yiyin Anshen Granule (YA) exerts sedative-hypnotic effects in a mouse model of sleep deprivation. DL-4-chlorophenylalanine(PCPA)-treated mice received intragastric administration of YA and pentobarbital sodium-induced sleep tests were conducted on days 7, 14, and 29. The levels of key neurotransmitters, cytokines and receptor protein associated with insomnia were measured using enzyme-linked immunosorbent assay (ELISA) and Western blot. Additionally, 16S ribosomal DNA (rDNA) sequencing was performed to assess the impact of YA on gut microbiota, focusing on species abundance and diversity. YA significantly shortened sleep latency (P < 0.01) and prolonged sleep duration (P < 0.01) in sleep-deprived mice, effectively improving circadian rhythm disturbances compared to the model group (MOD). Biochemical analysis revealed that YA restored abnormal neurotransmitter levels in brain tissue, increasing 5-hydroxytryptamine (5-HT), γ-aminobutyric acid (GABA), and γ-aminobutyric acid type A receptor α-1 subunit (GABAARα1) expression (P < 0.01) and reducing the glutamate (Glu)/GABA ratio (P < 0.01). Additionally, the levels of B-cell lymphoma 2 (BCL-2) and interleukin-6 (IL-6) expression were significantly decreased (P < 0.05, 0.01), while interleukin-1 beta (IL-1β) expression increased (P < 0.01). YA treatment also significantly increased gut microbiota abundance and diversity, with microbiome profiles in the YA group being closer than those of diazepam group (DZP) to the control group (CON). Notably, YA reversed the dysbiosis of high-abundance gut microbiota species associated with insomnia at both the family and genus levels (P < 0.05, 0.01). The results of the present study indicated that YA alleviates insomnia symptoms by regulating neurotransmitter and inflammatory cytokines levels, and restoring gut microbia balance. These mechanisms collectively contribute to shortening sleep latency, prolonging sleep duration, and improving sleep quality in a mouse model of insomnia.

Sleep-disordered breathing (SDB) is characterized by recurrent reductions or interruptions in airflow during sleep, termed hypopneas and apneas, respectively. SDB impairs sleep quality and is linked to substantive health issues including cardiovascular and metabolic disorders, as well as cognitive decline. Recent evidence suggests a link between gut microbiota (GM) composition and sleep apnea. Indeed, GM, a community of microorganisms residing in the gut, has emerged as a potential player in various diseases, and several studies have identified associations between sleep apnea and GM diversity along with shifts in bacterial populations. Additionally, the concept of "leaky gut," a compromised intestinal barrier with potentially increased inflammation, has emerged as another key player in the potential bidirectional relationship between GM and sleep apnea. One of the potential effectors could be extracellular vesicles (EVs) underlying gut-brain communication pathways that are relevant to sleep regulation and function. Thus, therapeutic implications afforded by targeting the GM or exosomes for sleep apnea management have surfaced as promising areas of research. This review explores current understanding of the relationship between GM, exosomes and sleep apnea, highlighting key research dynamics and potential mechanisms. A comprehensive review of the literature was conducted, focusing on studies investigating GM composition, intestinal barrier function and gut-brain communication in relation to sleep apnea.

Bailemian capsule (BLMC) is composed of lily bulb, thorny Acanthopanax root, and other traditional Chinese medicines; it is commonly used to treat insomnia in traditional Chinese medicine. However, the active ingredients and mechanisms of action that underlie this treatment ability have not been fully explored. Here, a liquid chromatography-tandem mass spectrometry method was developed to qualitatively analyse the exogenous BLMC components that directly entered the blood and several brain regions after administration of BLMC to mice. A total of 47 compounds that directly entered the blood, including isoleucine. Moreover, there were 33, 34, 36, and 27 compounds distributed in the hypothalamus, hippocampus, frontal cortex, and temporal cortex of the mice, respectively. Subsequently, this study integrated network pharmacology, metabolomics and gut microbiota analysis to explore potential mechanism of BLMC against insomnia. The network pharmacology results suggest that BLMC affects insomnia by modulating the glutamatergic synaptic pathway. And serum and hypothalamic metabolomics analysis indicates that BLMC mainly regulates the metabolic pathways of D-Glutamine and D-Glutamic acid metabolism, significantly upregulating the differential metabolite glutamic acid and downregulating glutamine. In addition, analysis of gut microbiota indicates a close relationship between norank_f_Desulfovibirosaceae and glutamic acid. This study systematically revealed for the first time the potential pharmacological components of BLMC in treating insomnia, and explored its mechanism of action from multiple perspectives, laying the foundation for further exploration of the mechanism of BLMC in treating insomnia.

Postpartum sleep disorder and mental disorders are common unpleasant conditions faced by women after delivery, and they have many adverse effects on both mothers and infants. It is unclear whether breast milk composition is affected by maternal sleep, psychological state, diet and gut microbiome. This study aims to explore the effects of these key factors on the functional protein components of breast milk.

With a prospective design, this pilot study included a total of 41 postpartum women. Breast milk and maternal faecal samples collected at 42 days and 3 months postpartum were tested by liquid chromatography-mass spectrometry and 16S RNA sequencing, respectively. Sleep state, psychological state and dietary intake data were also collected from the mothers with validated questionnaires.

In the early postpartum period, sleep disorders and depression were associated with a decrease in the functional proteins in breast milk. Disordered sleep was significantly negatively correlated with α-lactalbumin (cor = -0.578, p < 0.001), osteopontin (cor = -0.522, p < 0.01) and κ-casein (cor = -0.451, p < 0.01). Depression was negatively correlated with αs1-casein (cor = -0.422, p < 0.01), β-casein (cor = -0.317, p < 0.05) and casein (cor = -0.318, p < 0.05). In 3 months postpartum, most associations were disappeared. But a positive correlation was observed between β-casein (cor = 0.414, p < 0.01), casein (cor = 0.372, p < 0.05), total protein (cor = 0.376, p < 0.05) and depression, while a positive correlation was found between total protein (cor = 0.357, p < 0.05) and disordered sleep at 3 months postpartum. Faecal microbiome data illustrated that changes in the gut microbiome at early postpartum were associated with sleep disorders/depression, but not with the diet. Furthermore, functional pathway analysis revealed metabolic regulation in the amino acid synthesis and metabolic pathways associated with specific microbes was involved in the reduction of breast milk protein.

Sleep disorders/depression could lead to significant changes in breast milk profiles at 42 days postpartum. Maternal gut microbiome might affect breast milk protein composition through regulating amino acid synthesis and metabolic pathways.

BackgroundInsomnia is a common neurological disorder that exhibits connections with the gut microbiota; however, the exact causal relationship remains unclear. MethodsWe conducted a Mendelian randomization (MR) study to systematically evaluate the causal effects of genus-level gut microbiota on insomnia risk in individuals of European ancestry. Summary-level datasets on gut microbiota were sourced from the genome-wide association study (GWAS) of MiBioGen, while datasets on insomnia were obtained from the GWAS of Neale Lab and FinnGen. The primary analytical approach used was the inverse-variance weighted (IVW) method, supplemented by MR-Egger, maximum likelihood, MR-robust adjusted profile score, and weighted median. Sensitivity analyses were conducted to ensure robustness. ResultsThe microbial taxa Enterorhabdus, Family XIII AD3011 group, Paraprevotella, and Lachnospiraceae UCG004 were associated with an increased risk of insomnia, whereas Coprococcus1, Coprobacter, Desulfovibrio, Flavonifractor, Olsenella, Odoribacter, and Oscillibacter were linked to a decreased risk. Regarding the insomnia phenotype characterized by trouble falling asleep, the microbial taxon Eisenbergiella was correlated with an increased risk, while Haemophilus and the Eubacterium brachy group were associated with a reduced risk. Furthermore, for the insomnia phenotype characterized by waking too early, the microbial taxa Family XIII UCG001, Lachnospiraceae FCS020 group, and Olsenella were linked to an increased risk, whereas the Eubacterium brachy group and Victivallis were associated with a lower risk. The results remained robust across all sensitivity analyses. ConclusionOur MR study identified multiple genus-level gut microbial taxa that may exhibit potential causal effects on insomnia from a genetic perspective. These findings provide evidence supporting the theory of the microbiota-gut-brain axis and offer new insights into potential prevention and therapeutic targets for insomnia.

Sleep interacts reciprocally with the gut microbiota. However, mechanisms of the gut microbe-brain metabolic axis that are responsible for sleep behavior have remained largely unknown. Here, we showed that the absence of the gut microbiota can alter sleep behavior. Sleep deprivation reduced butyrate levels in fecal content and the hypothalamus in specific pathogen-free mice but not in germ-free mice. The microbial metabolite butyrate can promote sleep by modulating orexin neuronal activity in the lateral hypothalamic area in mice. Insomnia patients had lower serum butyrate levels and a deficiency in butyrate-producing species within the gut microbiota. Transplantation of the gut microbiota from insomnia patients to germ-free mice conferred insomnia-like behaviors, accompanied by a decrease in serum butyrate levels. The oral administration of butyrate rescued sleep disturbances in recipient mice. Overall, these findings reveal the causal role of microbial metabolic pathways in modulating insomnia-like behaviors, suggesting potential therapeutic strategies for treating sleep disorders.

The gut is susceptible to environmental pollutants and is a crucial barrier to exchanging internal and exterior substances in animals and humans. Intestinal microbiota plays vital roles in nutrition metabolism, synthesis of functional compounds, immune regulation, inflammation, and infection. Gut microbiota dysbiosis can induce intestinal physical barrier damage, trigger inflammation, and increase gut permeability. Intestinal barrier dysfunction facilitates the entry of pathogenic bacteria and harmful chemicals into the body through the blood circulation system, potentially causing neurotoxicity, hepatotoxicity, respiratory toxicity, growth inhibition, and even death. Herein, we overviewed the knowledge on the toxic effects of chemical pesticides on fish intestines and gut microbiota in the latest decade (2015-2025) and attempted to summarize the potential toxicological mechanisms. Chemical pesticide exposure can cause intestinal damage, impair immune function, and disrupt gut microbiota in fish. Gut microbial dysbiosis was strongly associated with intestinal injury. Alterations in gut microbiome metabolites, such as lipopolysaccharide, peptidoglycan, and short-chain fatty acids, have been linked to intestinal damage, inflammation, and changes in permeability. The mechanisms underlying intestinal injury in fish exposed to chemical pesticides included apoptosis, oxidative stress, and inflammation, which are mediated by reactive oxygen species pathways as well as death receptor and mitochondrial signaling pathways. Furthermore, pesticide-induced intestinal dysbiosis can cause neurotoxicity and hepatotoxicity through the microbiome-gut-brain/liver axis.

Investigating brain-heart-gut coupling during sleep is crucial for understanding the coordinated regulatory mechanisms of multiple systems during sleep. Non-invasive continuous physiological signal acquisition techniques have been widely applied in brain-heart dynamic assessment. However, current research on gut function primarily focuses on gut microbiota, with a lack of systematic investigation into the macroscopic dynamic changes of gut function. This study, therefore, based on multiple non-invasive physiological signals, aims to explore the dynamic changes and underlying mechanisms of brain-heart-gut coupling during sleep.

The study enrolled 24 healthy subjects, and collected electroencephalogram (EEG), electrocardiogram (ECG), and bowel sounds (BS) signals during sleep. Through signal processing and spectral analysis, power spectral values of each physiological signal in different frequency bands were extracted. The maximal information coefficient (MIC) method was employed to dynamically monitor and quantitatively analyze the coupling strength of brain-heart-gut during sleep.

The study revealed that the strength of brain-heart-gut coupling significantly varied with sleep stages, showing a gradual weakening trend as sleep deepened. In terms of heart-gut coupling (HGC), the coupling strength between the very low frequency (VLF) band of heart rate variability (HRV) and all BS-derived power sequences was significantly lower than other HRV frequency bands. Regarding brain-heart coupling (BHC), the EEG-beta band showed distinct sleep-stage-dependent coupling characteristics with HRV frequency bands, while the EEG-delta band exhibited higher coupling strength with HRV bands during non-rapid eye movement (NREM) sleep. Additionally, the coupling strength of HGC was significantly higher than that of BGC.

This study successfully achieved quantitative assessment of brain-heart-gut coupling during sleep based on continuous physiological signals, revealing specific patterns of coupling strength changes across different sleep stages. This research provides new methodological support for the diagnosis of sleep disorders and functional bowel diseases, holding significant theoretical value and clinical application prospects.

Gut microbiota (GM) alterations have been implicated in depression, potentially mediated via changes in the prefrontal cortex (PFC). However, the causal relationship and underlying biological mechanisms remain unclear.

Summary statistics from genome-wide association studies (GWAS) of 473 GM (n = 5959), depression (43,280 cases, 329,192 controls), and 3935 brain imaging-derived phenotypes (IDPs) (n = 33,224) were utilized. Univariable Mendelian randomization (MR) analyses examined the associations between (i) GM and depression, (ii) depression and GM, (iii) brain IDPs and depression, and (iv) GM and PFC-related IDPs. Multivariable MR (MVMR) assessed whether PFC structural phenotypes mediated the effect of GM on depression risk. Summary-data-based MR (SMR) identified potential genes and therapeutic targets. Single-cell RNA sequencing and bulk RNA data from GEO database about PFC tissue of depression patients were analyzed for biomarker expression and regulatory mechanisms. Target genes were validated in mice model through behavioral tests, RT-qPCR, and immunofluorescence analyses. Drug prediction and molecular docking explored potential therapeutic targets and traditional Chinese medicine.

The analysis identified 15 positive and 16 negative causal effects between GM and depression. Reverse MR analysis revealed 36 GM traits with reverse causality to depression. After excluding results with heterogeneity and pleiotropy, 11 PFC-related IDPs exhibited causal relationships with depression. MVMR adjustment for genetically predicted GM levels showed that the effects of PFC-related IDPs remained significant, indicating mediation of GM's effect on depression. Integration of GWAS and eQTL data identified 14 genes passing the SMR test. Differential expression of these genes was observed across cell types and between patients with depression and healthy controls. FARS2 and SLC25A21 were identified as potential therapeutic targets for depression, with protective effects shown in MR analysis (FARS2: OR: 0.892, 95 % CI: 0.813-0.971, P = 0.005; SLC25A21: OR: 0.924, 95 % CI: 0.851-0.997, P = 0.035). Reduced expression of FARS2 and SLC25A21 was validated in CUMS induced mice, along with depressive-like behaviors confirmed through behavioral tests. Molecular docking predicted Betanidin, Aloenin B, Rehmannioside D, and Vicenin-2 as potential drugs targeting both FARS2 and SLC25A21.

This study supports causal relationships between specific GM and depression, with PFC structures potentially mediating these effects. The findings provide insights into personalized depression treatment strategies and identify promising candidate targets and drugs for future research.

Parkinson's Disease (PD), a complex neurodegenerative disorder, is increasingly recognized as a systemic condition involving multi-organ interactions. Emerging evidence highlights roles of organ-brain axes (lung-, liver-, heart-, muscle-, bone-, and gut-brain) in PD pathogenesis. These axes communicate via neural, circulatory, endocrine, and inflammatory pathways, collectively driving neurodegeneration. For example, lung dysfunction in PD involves respiratory impairment and inflammatory signaling, while gut dysbiosis triggers α-synuclein aggregation via the vagus nerve. Such cross-organ interactions underscore PD's systemic nature, challenging traditional brain-centric models.

1. Decipher mechanisms linking peripheral organs (e.g., lung, gut) to PD via shared pathways. 2. Explore bidirectional organ-brain interactions (e.g., liver metabolism affecting neurotoxin clearance). 3. Propose multi-organ therapeutic strategies targeting integrated signaling networks. Key Scientific Concepts of Review. 1. Lung-Brain Axis: Respiratory dysfunction (motor impairment, inflammation) exacerbates neurodegeneration. 2. Liver-Brain Axis: Metabolic dysregulation alters neurotoxin clearance; drugs (e.g., levodopa) impact liver function. 3. Heart-Brain Axis: Autonomic dysfunction reduces cerebral blood flow; neuroendocrine changes promote α-synuclein pathology. 4. Muscle-Brain Axis: Neuromuscular/metabolic disruptions worsen motor symptoms. 5. Bone-Brain Axis: Bone-derived hormones (osteocalcin, OCN) and inflammation influence cognition. 6. Gut-Brain Axis: Dysbiosis drives α-synuclein misfolding; gut metabolites modulate neuroinflammation. Integrated Mechanisms: Shared pathways (neuroinflammation, oxidative stress) create a regulatory network, suggesting therapies targeting multi-organ crosstalk (e.g., probiotics, anti-inflammatory agents).

Ischemia-reperfusion injury (IRI) represents a pathophysiological phenomenon of profound clinical relevance that poses considerable threats to patient safety. IRI may manifest in a variety of clinical contexts including, but not limited to, sepsis, organ transplantation, shock, myocardial infarction, cerebral ischemia, and stroke. Critically, IRI exhibits complex interactions across different organs, with effects that surpass mere localized tissue damage. These impacts can amplify damage to both adjacent and remote organs through pathways such as the gut-brain axis and the gut-lung axis, facilitated by intricate signaling mechanisms. Noteworthy is the interaction between gut IRI and brain IRI, which involves sophisticated neuroendocrine, systemic, and immune mechanisms coordinated through the microbiome-gut-brain axis. This review seeks to delve into the intricate interactions between gut and brain IRI, viewed through the lens of the microbiota-gut-brain axis. It aims to assess its translational potential in clinical settings, provide a theoretical foundation for developing relevant therapeutic strategies, and pinpoint novel directions for research.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex disorder characterized by persistent fatigue and cognitive impairments, with emerging evidence highlighting the role of gut health in its pathophysiology. The main objective of this review was to synthesize qualitative and quantitative data from research examining the gut microbiota composition, inflammatory markers, and therapeutic outcomes of interventions targeting the microbiome in the context of ME/CFS.

The data collection involved a detailed search of peer-reviewed English literature from January 1995 to January 2025, focusing on studies related to the microbiome and ME/CFS. This comprehensive search utilized databases such as PubMed, Scopus, and Web of Science, with keywords including "ME/CFS," "Gut-Brain Axis," "Gut Health," "Intestinal Dysbiosis," "Microbiome Dysbiosis," "Pathophysiology," and "Therapeutic Approaches." Where possible, insights from clinical trials and observational studies were included to enrich the findings. A narrative synthesis method was also employed to effectively organize and present these findings.

The study found notable changes in the gut microbiota diversity and composition in ME/CFS patients, contributing to systemic inflammation and worsening cognitive and physical impairments. As a result, various microbiome interventions like probiotics, prebiotics, specific diets, supplements, fecal microbiota transplantation, pharmacological interventions, improved sleep, and moderate exercise training are potential therapeutic strategies that merit further exploration.

Interventions focusing on the gut-brain axis may help reduce neuropsychiatric symptoms in ME/CFS by utilizing the benefits of the microbiome. Therefore, identifying beneficial microbiome elements and incorporating their assessments into clinical practice can enhance patient care through personalized treatments. Due to the complexity of ME/CFS, which involves genetic, environmental, and microbial factors, a multidisciplinary approach is also necessary. Since current research lacks comprehensive insights into how gut health might aid ME/CFS treatment, standardized diagnostics and longitudinal studies could foster innovative therapies, potentially improving quality of life and symptom management for those affected.

Anxiety, a significant public health concern, frequently affects pediatric patients aged 6-18. This study seeks to examine the association between anxiety symptoms and gastrointestinal(GI) symptoms in patients within this age range who are visiting gastroenterology outpatient clinics. Additionally, we delve into whether sleep quality play a mediating role in this relationship. A cross-sectional analysis was conducted among 226 pediatric patients aged 6 and 18, who were recruited from the gastroenterology department of the Affiliated hospital of Xuzhou Medical University. Data were collected using a customized questionnaire that covered demographic information, clinical characteristics, and various self-assessment scales. To explore the association between GI symptoms and anxiety symptoms, a multivariate linear regression model was constructed. Additionally, we investigate the mediating role of sleep quality in this relationship. After accounting for key demographic and clinical factors, the intensity of GI symptoms exhibited a positive correlation with anxiety symptoms (β = 0.098, 95% CI: 0.070-0.137, p < 0.001). Furthermore, mediation analysis revealed that sleep quality partially mediated the relationship between the severity of GI symptoms and anxiety symptoms, contributing to a mediation effect of 11.13%. In pediatric patients aged 6-18, more severe GI symptoms were associated with a higher prevalence of anxiety symptoms, which in turn were linked to poorer sleep quality. It is advisable to incorporate assessments of sleep issues into the standard evaluation for pediatric patients in this age group visiting gastroenterology outpatient departments. Findings suggest that interventions targeting sleep quality may help manage GI symptoms, though longitudinal studies are needed to confirm causality.

This study aimed to explore the correlation between serum levels 1,3-β-D-glucan as a biomarker for gut microbiome imbalance and NLRP3 inflammasome/IL-1β axis activation and insomnia severity in humans with chronic insomnia disorder (CID). Blood samples were collected from 20 people diagnosed with CID based on the Pittsburgh Sleep Quality Index (PSQI) and video-polysomnography and 20 healthy individuals based on PSQI. 1,3-β-D-glucan, IL-1β, and NLRP3 protein serum levels were assayed using enzyme-linked immunosorbent assay (ELISA). 1,3-β-D-glucan, IL-1β, and NLRP3 protein serum concentrations in the CID group were significantly higher than in the control group. Also, we observed a significant positive correlation between the serum levels of these three factors in the CID group and a significant positive correlation between 1,3-β-D-glucan and insomnia severity index. Our findings suggest that 1,3-β-D-glucan may indicate gut microbiome imbalance in people with CID and may play an important role in the pathogenesis of chronic insomnia by activating the NLRP3/IL-1β inflammasome pathway. These results highlight the potential for dual therapeutic strategies targeting gut microbiota modulation and NLRP3 inflammasome inhibition to disrupt the neuroinflammatory cascade driving chronic insomnia.

Insomnia (difficulty falling or staying asleep) is a common issue among breast cancer survivors, significantly impacting their quality of life. Current treatments, primarily pharmacological and psychological, have limitations: the former often causes side effects, while the latter faces accessibility barriers. Long-snake moxibustion (LSM), a traditional Chinese medicine (TCM) technique, involves applying moxibustion along the governor vessel, which is an important meridian in TCM that plays a key role in regulating brain function. LSM is characterized by its minimal side effects, ease of application, and cost-effectiveness, with preliminary studies supporting its potential for treating insomnia. This study aims to further investigate the therapeutic effectiveness of LSM in alleviating insomnia among breast cancer survivors and to explore its underlying mechanisms.

This single-center, rater-masked, randomized controlled trial will enroll 100 breast cancer survivors with chronic insomnia, who will be randomly assigned in a 1:1 ratio to either the LSM group or a waitlist control group. During the 4-week treatment period, all participants will receive standard care, with the LSM group additionally receiving LSM treatment twice a week. The primary efficacy outcome is the change in Insomnia Severity Index (ISI) score at the end of the intervention. Secondary outcomes include changes in hypnotic medication use, Pittsburgh Sleep Quality Index (PSQI) scores, Piper Fatigue Scale (PFS) scores, and Functional Assessment of Cancer Therapy-Breast (FACT-B) scores. Mechanistic evaluations will assess serum biochemical markers, gut microbiota composition, and metabolomic profiles.

If proven effective, this trial will provide critical clinical evidence supporting LSM as a viable and accessible treatment for insomnia among breast cancer survivors. The findings could influence clinical practice by offering a non-pharmacological treatment option, improving patient outcomes, and reducing dependence on pharmacological interventions. Furthermore, exploring the underlying mechanisms may enhance our understanding of how LSM works, paving the way for future research.

http://itmctr.ccebtcm.org.cn/, identifier ITMCTR2024000578.

As a phytotherapeutic agent with historical applications in epilepsy management, Acorus tatarinowii Schott (ATS) remains pharmacologically enigmatic, particularly regarding its pathophysiological mechanisms. This knowledge gap significantly hinders the clinical application of ATS-based treatments. To explore the potential of ATS in combating epileptogenesis, we utilized a pentylenetetrazole (PTZ)-induced chronic epilepsy rat model. Brain metabolomic analysis was performed by ultra-performance liquid chromatography coupled with mass spectrometry (UPLC/MS). Principal component analysis (PCA) and orthogonal projections to latent structures-discriminant analysis (OPLS-DA) were performed for screening differential metabolites. Gut microbiota composition was analyzed through 16S rRNA gene sequencing and examined using Spearman correlation analysis. The results show that oral ATS (50 mg/kg) significantly improved the seizure latency and pathology of rats with epilepsy. Ascorbate and aldarate metabolism, glycerophospholipid metabolism, arachidonic acid metabolism, and intestinal flora were crucial for ATS's ability to counteract epilepsy. The therapeutic effects of ATS against epilepsy were investigated with brain metabolomics and gut microbiota analysis, providing the basis for further comprehensive research.

The intricate relationship between sleep disorders and hearing loss emerges as a burgeoning field of scholarly inquiry. Numerous studies have illuminated a potential correlation between the two, affecting the quality of life and overall health of individuals. Hearing loss, or auditory impairment, serves as a critical indicator of physiological dysfunction, casting a pall over the daily existence and professional endeavors of those affected, potentially leading to irreversible deafness if left untreated. Sleep disorders may cause physical and psychological changes that further affect hearing, while auditory dysfunction may detrimentally impact sleep experienced by individuals. Although certain studies have failed to find a direct link between sleep duration and hearing loss, it is evident that sleep-related issues do increase the risk of hearing loss. Thus, understanding the relationship between sleep disorders and hearing loss, alongside the underlying mechanisms, will help establish interventions aimed at enhancing sleep quality and safeguarding auditory health. This systematic review endeavors to elucidate the correlation between sleep disorders and hearing loss, offering valuable insights and guidance for future basic research and clinical applications.

The Enteric Nervous System (ENS), often called the "second brain," is a complex network of neurons and glial cells within the gastrointestinal (GI) tract. It functions autonomously while maintaining close communication with the central nervous system (CNS) via the gut-brain axis (GBA). ENS dysfunction plays a crucial role in neurodegenerative and neurodevelopmental disorders, including Parkinson's disease, Alzheimer's disease, and autism spectrum disorder. Disruptions such as altered neurotransmission, gut microbiota imbalance, and neuroinflammation contribute to disease pathogenesis. The GBA enables bidirectional communication through the vagus nerve, gut hormones, immune signaling, and microbial metabolites, linking gut health to neurological function. ENS dysregulation is implicated in conditions like irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), influencing systemic and CNS pathology through neuroinflammation and impaired barrier integrity. This review highlights emerging therapeutic strategies targeting ENS dysfunction, including prebiotics, probiotics, fecal microbiota transplantation (FMT), and vagus nerve stimulation, which offer novel ways to modulate gut-brain interactions. Unlike previous perspectives that view the ENS as a passive disease marker, this review repositions it as an active driver of neurological disorders. By integrating advances in ENS biomarkers, therapeutic targets, and GBA modulation, this article presents a paradigm shift-emphasizing ENS dysfunction as a fundamental mechanism in neurodegeneration and neurodevelopmental disorders. This perspective paves the way for innovative diagnostics, personalized gut-targeted therapies, and a deeper understanding of the ENS's role in brain health and disease.

Insomnia, a prevalent sleep disorder, significantly impacts global health. While Western medications provide temporary relief, their risks of dependency and cognitive impairment have spurred the search for safer alternatives. Traditional Chinese Medicine (TCM) offers a promising approach to treating insomnia by focusing on harmonizing the balance of Yin and Yang and the functions of internal organs. This review explores recent research advances in TCM for insomnia treatment, integrating classical theories with modern scientific understanding of key pathological mechanisms, including neurotransmitter regulation (GABA, monoamines), immune-inflammatory responses, the HPA axis, and interactions with the gut microbiota. Growing clinical evidence supports the effectiveness of classical TCM prescriptions and treatments like acupuncture in improving sleep quality, particularly when combined with Western medications to enhance efficacy and reduce dependency. However, TCM also has its limitations. Future research directions should focus on modernizing TCM applications, addressing comorbidities associated with insomnia, exploring the role of gut microbiota, and optimizing medicinal and edible homologous products. By integrating traditional knowledge with cutting-edge technologies, TCM holds great potential for advancing personalized and effective insomnia treatments globally.

Non-operative spinal infections (NOSI) are caused by tuberculosis, brucella, and other specific bacteria. The etiology of the disease is insidious, the onset is slow and the diagnosis and treatment are difficult. Identifying the factors associated with spinal infection and early intervention can reduce the occurrence of the disease. At present, the research mainly focuses on the accurate diagnosis and treatment of spinal infection, and there are few studies on the prevention of spinal infection. The concept of "preventive treatment of diseases" in traditional Chinese medicine may help identify the causes and reduce the occurrence of NOSI.

To determine the association of age, bowel movements, and sleep patterns with NOSI.

Data of 69 NOSI patients and 84 healthy controls in a tertiary hospital from January 2019 to June 2024 were collected. Patients with NOSI had imaging evidence (magnetic resonance imaging) of spinal infections (including infections caused by tuberculosis, brucopathy, and other pathogens) and had no history of spinal surgery in the last 1 year were included in the analysis. Patients with spinal infection due to spinal surgery are excluded in the study. Data including age, sex, place of residence, sleeping status, and bowel movements were collected. SPSS22.0 was used for correlation analysis of all data.

The mean age of the NOSI group and the control group was 63.55 ± 14.635 years and 59.18 ± 17.111 years, respectively, without statistical difference (P = 0.096). There was also no statistically significant difference in gender between the two groups. In the NOSI group, 45 (65.22%) were over 60 years old, and 44 (63.77%) were rural residents. Compared with the control group, the NOSI group had more patients with sleep disorder and defecation disorder, accounting for 69.57% and 68.12%, respectively, with significant statistical difference (both P < 0.001). Regression analysis showed that defecation and sleep disorders were closely related to NOSI (both P < 0.001).

Most patients with NOSI are older and have sleep disorders and abnormal defecation.

The microbiome, especially the gut microbiome, contributes to the regulation, etiology, and pathogenesis of sleep disorder. However, limited evidence regarding the oral microbiome's role in sleep disorder. Therefore, this study aimed to investigate the association between sleep disorder and oral microbial diversity and whether oral microbiota is associated with all-cause mortality in people with sleep disorder.

The study included 4,729 individuals in the National Health and Nutrition Examination Survey (NHANES) from 2009 to 2012 and mortality data until 2019. Sleep disorder was assessed by structured questionnaire. The oral microbiome was characterized by 16 S ribosomal RNA gene sequencing. Logistic regression models were conducted to quantify the association of α-diversity with different sleep status controlling for potential confounding variables, and principal coordinate analysis along with permutational multivariate analysis of variance for β-diversity. The association between the oral microbiome and all-cause mortality was assessed using Cox proportional hazard models.

The α-diversity showed that a lower number of operational taxonomic units (OTUs) (adjusted odds ratio [aOR] = 0.996; 95% confidence interval [CI] = 0.994-0.998), less Faith's phylogenetic diversity (aOR = 0.954, 95% CI = 0.934-0.975), and a lower Shannon-Weiner index (aOR = 0.854, 95% CI = 0.772-0.944) were associated with sleep disorder. β-diversity revealed different oral microbiome communities between the two groups, as measured by the Bray-Curtis dissimilarity (R2 = 0.358%, P = 0.001), unweighted UniFrac distance (R2 = 0.450%, P = 0.001) and weighted UniFrac distance (R2 = 0.709%, P = 0.001). Furthermore, the OTUs (odds ratio [OR] = 0.999; 95% CI = 0.998-0.999; P < 0.05), Faith's phylogenetic diversity (OR = 0.987; 95% CI = 0.975-0.998; P < 0.05), Shannon-Weiner index (OR = 0.924; 95% CI = 0.873-0.979; P < 0.05), and the inverse Simpson index (OR = 0.553; 95% CI = 0.306-0.997; P < 0.05) were all associated with a significant increase in the risk of all-cause death in participants with sleep disorder.

Intra-population richness, inter-population dispersion, and the phylogenetic diversity of the oral microbiome have all been linked to sleep disorder and all-cause mortality. Overall, these results will help to better understand the etiology and pathogenesis of sleep disorder. Further studies are required to determine the mechanisms underlying the role of microbiome in the pathogenesis of sleep disorder.

Shuangxia Decoction (SXD), evolved from " Banxia Shumi Decoction", is composed of Pinellia ternata (Thunb.) Makino and Prunella vulgarisl. SXD has been used to treat insomnia and is considered the first traditional Chinese herbal formula developed specifically for the treatment of insomnia.

This study aimed to investigate the mechanism underlying SXD's effects against insomnia using multi-omics technologies.

Network pharmacology was employed to predict the active components and core targets of SXD in treating insomnia, utilizing 17 active compounds. The pharmacodynamics of SXD were further validated in sleep-deprived mice. UPLC-QE-Orbitrap-MS was utilized to analyze serum metabolomics and hypothalamic tissue metabolomics of the sleep-deprived mice, revealing the biological mechanism of SXD against sleep deprivation. Rosmarinic acid (RA), a representative component of SXD, was selected to further investigate its anti-sleep deprivation mechanism, including intestinal ROS activity assays, intestinal metabolite analysis, serum metabolomics, gut microbiota analysis, and western blotting.

Through network pharmacology analysis, three active compounds and four targets were identified as key contributors to the therapeutic effects of SXD on insomnia. In the sleep deprivation (SD) model regulated by SXD, metabolomics studies revealed 28 differential serum metabolites and 20 differential metabolites in hypothalamic tissues. Among these, three shared differential metabolites (Hypoxanthine, Pyrroline hydroxycarboxylic acid, Hydroxyphenyllactic acid) and two critical metabolic pathways (purine metabolism and arginine and proline metabolism) were identified. In the SD model regulated by RA, varying doses of RA effectively reduced SD-induced ROS accumulation in both the small and large intestines. Analysis of RA metabolites in the intestines revealed 57 putative metabolites, most of which were oxidized products. Serum metabolomics analysis of RA against SD showed 58 differential metabolites, with purine metabolism and phenylalanine metabolism pathways being notably involved. Hypoxanthine was identified as a potential marker for clinical sleep deprivation by integrating serum and hypothalamic tissue metabolomics data from SXD and serum metabolomics data from RA. 16S rRNA sequencing demonstrated that SD significantly altered the abundance of eight gut microbiota species. RA exhibited a restorative effect on specific imbalanced gut microbiota, independent of dosage. Western blotting analysis revealed that RA preserved intestinal epithelial integrity by modulating the expression of tight junction proteins, including ZO-1, occludin and claudin. Meanwhile, RA effectively alleviated SD-induced oxidative stress by activating the Nrf2 signaling pathway, promoting nuclear translocation of Nrf2 and increasing the expression of its downstream antioxidant proteins HO-1 and NQO-1 in the small and large intestines.

Our study demonstrates that SXD has significant efficacy in alleviating SD. RA, as the representative compound of SXD, can eliminate the accumulation of intestines ROS in SD mice and improve gut microbiota imbalance caused by oxidative stress by upregulating tight junction proteins ZO-1, Occludin, and Claudin, and regulating the Nrf2 signaling pathway. Furthermore, hypoxanthine has been identified as a promising and reliable biomarker for SD.

Research has suggested an interaction between gut microbiota and sleep, yet the causal relationships between gut microbiota, metabolites, and sleep disorders remain unclear. This study aims to uncover these relationships.

We obtained genome-wide data for 196 gut microbiota (GM) species (N = 18,340), 1,400 metabolites (N = 8,299), and sleep disorders (N = 361,194). Mendelian randomization(MR) analyses were conducted using the Inverse Variance Weighted (IVW) method, MR-Egger, Weighted Median method, Weighted Mode method, and Simple Mode method to infer causality. The IVW method was used for primary analysis results. Significant microbiota and causal metabolites were further analyzed to clarify the associations between the three. All results were tested for heterogeneity, pleiotropy, and sensitivity to assess the stability of the findings.

The Mendelian randomization results revealed causal relationships between four gut microbiota species and sleep disorders: Genus.Dorea, Genus.Parasutterell, Genus.Slackia, and Order.Bacillales. Additionally, we identified 39 causal metabolites Related to sleep disorders, with 7 of these being associated with 3 causal microbiota species at the genus level. All results showed no heterogeneity or horizontal pleiotropy.

Through two-sample Mendelian randomization studies, we identified three gut microbiota species at the genus level genetically linked to sleep disorders through seven plasma metabolites, revealing causal relationships between these three factors. These biomarkers provide new insights into the mechanisms of sleep disorders and may contribute to their prevention, diagnosis, and treatment.

Sleep is an essential homeostatic process that undergoes dynamic changes throughout the lifespan, with distinct life stages predisposed to specific sleep pathologies. Similarly, the gut microbiome also varies with age, with different signatures associated with health and disease in the latest decades of life. Emerging research has shown significant cross-talk between the gut microbiota and the brain through several pathways, suggesting the microbiota may influence sleep, though the specific mechanisms remain to be elucidated. Here, we critically examine the existing literature on the potential impacts of the gut microbiome on sleep and how this relationship varies across adulthood. We suggest that age-related shifts in gut microbiome composition and immune function may, in part, drive age-related changes in sleep. We conclude with an outlook on the therapeutic potential of microbiome-targeted interventions aimed at improving sleep across adulthood, particularly for individuals experiencing high stress or with sleep complaints.

Sleep disorders have become one of the most prevalent neuropsychiatric disorders in recent years. This study aimed to investigate the effects of postbiotics derived from selected lactic acid bacteria on anhedonia and sleep disorders in chronic restraint stress (CRS)-induced mice, as well as their potential mechanisms. Mice were orally administered normal saline, low, medium, or high doses of postbiotics for 30 days, with CRS applied from days 1 to 21. The medium dose of postbiotics significantly increased the sucrose preference index, and the high dose of postbiotics significantly increased sleep duration. Postbiotic treatment effectively restored the diversity and composition of the gut microbiota to levels comparable to those observed in the vehicle (Veh) group. Furthermore, low and medium doses of postbiotics significantly reduced serum corticosterone levels, and medium and high doses significantly reduced serum IL-1β levels. Additionally, postbiotics administration significantly increased glutamate and GABA levels in both the prefrontal cortex and hypothalamus, as well as GABA levels in the feces. These results indicate that postbiotics alleviate CRS-induced anhedonia and sleep disorders in a dose-dependent manner. This effect may be mediated through the restoration of homeostasis in the MGB axis, HPA axis, inflammation pathways, and neurotransmitter balance.

Limited epidemiological study has examined the association between rotating shift work and risk of irritable bowel syndrome (IBS). This study aimed to investigate the association between shift work and risk of IBS and explore the potential mediating factors for the association.

A total of 268,290 participants from the UK Biobank were included. Cox proportional hazards model was used to examine the associations between shift work and the incidence of IBS. The mediation analyses were performed to investigate the mediating effects.

Participants engaged in always/usually shift work showed a significantly increased risk of developing IBS (HR: 1.12, 95% CI: 1.03-1.23). Joint analysis indicated that, participants with both always/usually shift work and inadequate sleep duration had a 54% increased risk of IBS (HR: 1.54, 95% CI: 1.35-1.82) compared to those with adequate sleep duration and never/rarely shift work; while participants with both always/usually shift work and insomnia-always had a 65% increased risk of IBS (HR: 1.65, 95% CI: 1.43-1.90) compared to those with never/rarely shift work and never/sometimes insomnia. Mediation analysis revealed that sleep quality and anxiety/depression partially mediated the relationship between shift work and IBS incidence, contributing 16.1% (6.8-25.4%) and 3.6% (0.4-6.8%) of the mediation effect, respectively.

This study found that participants with always/usually shiftwork status had significantly increased risk of IBS, and this association may partially be mediated by anxiety/depression and sleep quality. Moreover, inadequate sleep duration and usually insomnia may intensify the effect of rotating shift work on the risk of incident IBS.

The etiology of psychiatric disorders is complex and results from intricate interactions among multiple neurobiological, psychological, environmental, and genetic factors. Furthermore, the roles of gut microbiome dyshomeostasis in their pathogeneses are just beginning to be uncovered, adding to another level of complexity. In recent years, significant efforts have been directed toward discovering multimodal yet safe therapeutics to counteract psychological deficits. Rosmarinic acid (RA), a polyphenol found in several medicinal herbs, has received considerable attention as a potential multifaceted therapeutic agent, particularly for neuropsychiatric conditions. In order to critically evaluate this aspect, data was compiled and consolidated after extensive searches on scholarly databases like PubMed, Google Scholar, and Web of Science. Peer-reviewed publications which focused on RA as a therapeutic agent for psychiatric disorders were included regardless of the year of publication and country of origin. Based on pre-clinical and clinical evidence, this review delves into the various mechanistic aspects of the antidepressant, anxiolytic, and sleep-promoting functions of RA. The beneficial effects of RA on the gut-microbiome-brain (GMB) axis and their implications for the regulation of neuroprotective pathways are also discussed, with a particular focus on exploiting them to ameliorate neuropsychiatric conditions. Our assessment indicated that RA is a multimodal neuroprotectant against psychiatric conditions and beneficially influences a plethora of targets related to redox, inflammatory, synaptic, cell death, neurotrophic, and cell signaling pathways. As a dietary agent, RA may also be relevant in favorably altering the GMB axis, indicating its prospects as a potential multimodal adjuvant therapeutic agent in regulating the pathogenic mechanisms underlying neuropsychiatric conditions. However, more extensive clinical studies are required to ascertain the neuromodulatory actions of RA in neuronal pathophysiologies, including psychiatric ailments.

A deeper understanding of the communication network between the gut microbiome and the central nervous system, termed the gut-brain axis (GBA), has revealed new potential targets for intervention to prevent the development of neurodegenerative disease associated with tramatic brain injury (TBI). This review aims to comprehensively examine the role of GBA post-traumatic brain injury (TBI).

The GBA functions through neural, metabolic, immune, and endocrine systems, creating bidirectional signaling pathways that modulate brain and gastrointestinal (GI) tract physiology. TBI perturbs these signaling pathways, producing pathophysiological feedback loops in the GBA leading to dysbiosis (i.e., a perturbed gut microbiome, impaired brain-blood barrier, impaired intestinal epithelial barrier (i.e., "leaky gut"), and a maladaptive, systemic inflammatory response. Damage to the CNS associated with TBI leads to GI dysmotility, which promotes small intestinal bacterial overgrowth (SIBO). SIBO has been associated with the early stages of neurodegenerative conditions such as Parkinson's and Alzheimer's disease. Many of the bacteria associated with this overgrowth promote inflammation and, in rodent models, have been shown to compromise the structural integrity of the intestinal mucosal barrier, causing malabsorption of essential nutrients and further exacerbating dysbiosis. TBI-induced pathophysiology is strongly associated with an increased risk of neurodegenerative diseases, including Parkinson's and Alzheimer's diseases, which represents a significant public health burden and challenge for patients and their families. A healthy gut microbiome has been shown to promote improved recovery from TBI and prevent the development of neurodegenerative disease, as well as other chronic complications. The role of the gut microbiome in brain health post-TBI demonstrates the potential for microbiome-targeted interventions to mitigate TBI-associated comorbidities. Promising new evidence on prebiotics, probiotics, diet, and fecal microbiota transplantation may lead to new therapeutic options for improving the quality of life for patients with TBI. Still, many of these preliminary findings must be explored further in clinical settings. This review covers the current understanding of the GBA in the setting of TBI and how the gut microbiome may provide a novel therapeutic target for treatment in this patient population.

Sleep deprivation research (SDR) has undergone substantial transformations in the aftermath of the COVID-19 pandemic. This comprehensive study explores the SDR's evolving trends, hotspots, and conceptual structure in the post-COVID-19 era. Using bibliometric analysis with VOSviewer and Bibliometrix software, we examined the SDR publications from January 2020 to December 2023. Core sources were identified using Bradford law, and a dataset of 4578 English-based data-driven studies was retrieved from the Scopus database. Our analysis revealed a remarkable annual growth rate of 37.92% in SDR from 2020 to 2023, indicating a heightened research focus in this domain. Among prolific authors, Shao emerged as a key contributor, while Sleep ranked prominently as a leading publication venue. The United States and China have emerged as the most impactful countries for advancing SDR research. Uncovering the most cited documents sheds light on various focal points within SDR, including sleep duration, mental health implications, cardiovascular events, the impact of COVID-19 on sleep patterns, dementia, resilience in children, and sleep patterns among preschoolers. Noteworthy keywords that emerged from the analysis encompassed "sleep deprivation," "depression," "insomnia," "COVID-19," "anxiety," "fatigue," and "obesity." Using a thematic mapping approach, we delineated distinct themes characterized by niche, basic, emerging, and declining patterns. Clusters of SDR research were observed in areas such as "Fatigue," "Sleep apnea," "Sleep," "Sleep deprivation," "Migraine," "Caffeine," and "Recovery." Furthermore, trending themes in SDR encompassed "Sleep disturbance," "excessive daytime sleepiness," and "Gamma-Aminobutyric Acid." These comprehensive findings provide valuable insights into the current landscape of SDR, illuminating emerging trends, identifying hotspots, and offering directions for future research in this critical field.

As a traditional drug-food homologous plant, Dendrobium officinale is widely recognized for its nutritional and medicinal value. Specifically, D. officinale polysaccharide (DOP) has garnered attention as a potential prebiotic for its protective effects on gut microbiota and the nervous system. However, the underlying mechanism by which DOP improves cognitive dysfunction in Alzheimer's disease (AD) remains unclear. This study intends to elucidate the beneficial effects of DOP on AD mice from the perspectives of metabolomics and the intestinal microbiome. The results showed that DOP significantly ameliorated cognitive dysfunction, attenuated hippocampal neuronal damage and Aβ plaque deposition, and restored intestinal barrier integrity in AD mice. The antibiotic-cocktail-induced germ-free mouse model confirmed that the neuroprotective effect of DOP was dependent on gut microbiota. Further investigations demonstrated that DOP influenced the composition of gut microbiota and restored its diversity. Additionally, DOP reshaped metabolic profile disorders in AD mice and increased the short-chain fatty acids (SCFAs) content. Correlation analysis further highlighted that specific gut microbiota was associated with the metabolism of AD mice. In conclusion, this study sheds light on the positive impact of DOP in reshaping the gut microbiota and enhancing cognitive function, offering important perspectives for the possible advancement and utilization of DOP.

There is growing evidence that sleep deprivation promotes cancer progression. In addition, colon cancer patients often experience sleep deprivation due to factors such as cancer pain and side effects of treatment. The occurrence of liver metastases is an important factor in the mortality of colon cancer patients. However, the relationship between sleep deprivation and liver metastases from colon cancer has not been elucidated.

A sleep deprivation liver metastasis model was constructed to evaluate the effect of sleep deprivation on liver metastasis of colon cancer. Subsequently, mice feces were collected for untargeted metabolomics to screen and identify the key mediator, Kynurenic acid (KynA). Furthermore, HILPDA was screened by transcriptomics, and its potential mechanism was explored through ChIP, co-IP, ubiquitination experiments, phenotyping experiments, etc. RESULTS: Sleep deprivation promotes liver metastases in colon cancer. Functionally, sleep deprivation aggravates lipid accumulation and decreases the production of the microbiota metabolite KynA. In contrast, KynA inhibited colon cancer progression in vitro. In vivo, KynA supplementation reversed the promoting effects of sleep deprivation on liver metastases from colon cancer. Mechanistically, KynA downregulates the expression of P4HA2 to promote the ubiquitination and degradation of HIF-1α, which leads to a decrease in the transcription of HILPDA, and ultimately leads to an increase in lipolysis of colon cancer cells.

Our findings reveal that sleep deprivation impairs intracellular lipolysis by KynA, leading to lipid droplets accumulation in colon cancer cells. This process ultimately promotes colon cancer liver metastasis. This suggests a promising strategy for colon cancer treatment.

The gut microbiome plays a fundamental role in mental health, influencing mood, cognition, and emotional regulation through the gut-brain axis. This bidirectional communication system connects the gastrointestinal and CNS, facilitated by microbial metabolites, neurotransmitters, and immune interactions. Recent research highlights the association between gut dysbiosis and psychiatric disorders, including anxiety, depression, and stress-related conditions. Key findings indicate that altered microbial diversity, decreased short-chain fatty acid (SCFA) production, and increased neuroinflammation contribute to mental health disturbances. This paper explores the mechanism linking the gut microbiome to brain function, including microbial neurotransmitter synthesis, vagus nerve signaling, and hypothalamic-pituitary-adrenal (HPA) axis modulation. Additionally, it evaluates the potential of microbiome-targeted interventions, such as probiotics, prebiotics, dietary modifications, and fecal microbiota transplantation (FMT), in alleviating psychiatric symptoms. Microbiome sequencing and bioinformatics advances further support the development of personalized microbiome-based mental health interventions. Despite promising evidence, challenges such as inter-individual variability, methodological inconsistencies, and the need for longitudinal studies remain. Future research should focus on standardizing microbiome assessment techniques and optimizing therapeutic applications. Integrating precision psychiatry with microbiome-based diagnostics holds immense potential in transforming mental health treatment.

Sleep is essential for brain development and overall health, particularly in children with neurodevelopmental disorders (NDDs). Sleep disruptions can considerably impact brain structure and function, leading to dysfunction of neurotransmitter systems, metabolism, hormonal balance and inflammatory processes, potentially contributing to the pathophysiology of NDDs. This Review examines the prevalence, types and mechanisms of sleep disturbances in children with NDDs, including autism spectrum disorder, attention-deficit hyperactivity disorder and various genetic syndromes. Common sleep disorders in these populations include insomnia, hypersomnia, circadian rhythm disorders, sleep-related breathing disorders and parasomnias, with underlying factors often involving genetic, neurobiological, environmental and neurophysiological influences. Sleep problems such as insomnia, night awakenings and sleep fragmentation are closely linked to both internalizing symptoms such as anxiety and depression, and externalizing behaviours such as hyperactivity and aggression. Assessment of sleep in children with NDDs presents unique challenges owing to communication difficulties, comorbid conditions and altered sensory processing. The Review underscores the importance of further research to unravel the complex interactions between sleep and neurodevelopment, advocating for longitudinal studies and the identification of predictive biomarkers. Understanding and addressing sleep disturbances in NDDs is crucial for improving developmental outcomes and the overall quality of life for affected individuals and their families.

Sleep deprivation is a prevalent issue in contemporary society, with significant ramifications for both physical and mental well-being. Emerging scientific evidence illuminates its intricate interplay with the gut-brain axis, a vital determinant of neurological function. Disruptions in sleep patterns disturb the delicate equilibrium of the gut microbiota, resulting in dysbiosis characterized by alterations in microbial composition and function. This dysbiosis contributes to the exacerbation of neurological disorders such as depression, anxiety, and cognitive decline through multifaceted mechanisms, including heightened neuroinflammation, disturbances in neurotransmitter signalling, and compromised integrity of the gut barrier. In response to these challenges, there is a burgeoning interest in therapeutic interventions aimed at restoring gut microbial balance and alleviating neurological symptoms precipitated by sleep deprivation. Probiotics, dietary modifications, and behavioural strategies represent promising avenues for modulating the gut microbiota and mitigating the adverse effects of sleep disturbances on neurological health. Moreover, the advent of personalized interventions guided by advanced omics technologies holds considerable potential for tailoring treatments to individualized needs and optimizing therapeutic outcomes. Interdisciplinary collaboration and concerted research efforts are imperative for elucidating the underlying mechanisms linking sleep, gut microbiota, and neurological function. Longitudinal studies, translational research endeavours, and advancements in technology are pivotal for unravelling the complex interplay between these intricate systems.

Circadian rhythms are intrinsic molecular mechanisms that synchronize biological functions with the day/night cycle. The mammalian gut is colonized by a myriad of microbes, collectively named the gut microbiota. The microbiota impacts host physiology via metabolites and structural components. A key mechanism is the modulation of host epigenetic pathways, especially histone modifications. An increasing number of studies indicate the role of the microbiota in regulating host circadian rhythms. However, the mechanisms remain largely unknown. Here, we summarize studies on microbial regulation of host circadian rhythms and epigenetic pathways, highlight recent findings on how the microbiota employs host epigenetic machinery to regulate circadian rhythms, and discuss its impacts on host physiology, particularly immune and metabolic functions. We further describe current challenges and resources that could facilitate research on microbiota-epigenetic-circadian rhythm interactions to advance our knowledge of circadian disorders and possible therapeutic avenues.

This study aimed to investigate the alterations in sleep quality and sleep patterns among military personnel at altitudes ranging from 1500 to 4500 m, as well as the associated factors influencing their sleep.

This study employed a longitudinal prospective survey conducted over a period of six months, from November 2023 to June 2024. A total of 90 soldiers were recruited for participation. Initially, demographic data and sleep conditions were collected through a questionnaire administered to participants at an altitude of 1,500 m. Subsequently, participants were monitored continuously to gather data over seven days at an altitude of 4,500 m, specifically during the 7 days of the 6-month survey period), and the 1st month at an altitude of 4,500 m (on the 1st month of the six-month survey period. Spearman's rank correlation was utilized to investigate the relationships among sleep quality, gastrointestinal symptoms, and mood states.

The total score of the Pittsburgh Sleep Quality Index (PSQI) exhibited an increase, indicating impaired sleep quality among soldiers stationed at an altitude of 4,500 m for durations 7 days, 1 month, 3 months, and 6 months. Notably, after 7 days of soldiers, there was a significant gradual in the number of military soldiers experiencing gastrointestinal symptoms, such as diarrhea, abdominal distention, and constipation, which subsequently stabilized with prolonged exposure to the altitude. Furthermore, a significant rise in the incidence of depression was observed after days of rapid exposure 4,500 above sea level, and the emotional state of military personnel tended to tend towards mild depression over the duration of time Correlation. Correlation analysis showed that the PSQI score was closely related to the Athens Insomnia Scale(AIS) total score, Epworth Sleepiness Scale(ESS) total score, Self-Rating Anxiety Scale(SAS) total score, Self-Rating Depression Scale(SDS) total score, difficulty in falling asleep, easy to wake up or wake up early at night, poor breathing and snoring (on the 1st month, the 3rd month and the 6th month at the altitude of 4500 m respectively: rs = 0.868, 0.648, 0.483, 0.459, 0.472, 0.364, 0.613, 0.75; rs = 0.856, 0.521, 0.481, 0.354, 0.768, 0.720, 0.511, 0.535; rs = 0.756, 0.490, 0.496, 0.352, 0.708, 0.737, 0.424, 0.408, p < 0.01 or p < 0.05); Positively correlated with heart rate (at 4500 m 7 days at altitude: rs = 0.233, p = 0.027), diarrhea (at 4500 m 1-month at altitude: rs = 0.237) bloating and constipation (at 4500 m 1 month and 3months respectively: rs = 0.472; rs = 0.364; rs = 0.341, 0.273, p < 0.05); and with age, sex, marital status, education were significantly positive correlation (rs = 0.463, 0.251, 0.255, 0.230, p < 0.05).

The impaired sleep quality, gastrointestinal symptoms, and anxiety and depression in military personnel changed with the extension of the time of stationing at 4500 m altitude, which was most prominent when stationed at high altitude for 7 days; the sleep quality of those stationed at high altitude had a close relationship with the gastrointestinal symptoms, the type of sleep(insomnia and drowsiness), and the heart rate, but it varied with the duration of the stationing at high altitude; our study provides new information for the prevention of sleep disturbance, gastrointestinal symptoms, and negative emotions in high-altitude military personnel.

Parkinson's disease (PD) and insomnia are prevalent neurological disorders, with emerging evidence implicating tryptophan (TRP) metabolism in their pathogenesis. However, the precise mechanisms by which TRP metabolism contributes to these conditions remain insufficiently elucidated. This study explores shared tryptophan metabolism-related genes (TMRGs) and molecular mechanisms underlying PD and insomnia, aiming to provide insights into their shared pathogenesis. We analyzed datasets for PD (GSE100054) and insomnia (GSE208668) obtained from the Gene Expression Omnibus (GEO) database. TMRGs were obtained from the Molecular Signatures Database (MSigDB) and the Genecards database. Tryptophan metabolism-related differentially expressed genes (TM-DEGs) were identified by intersecting TMRGs with shared differentially expressed genes (DEGs) from these datasets. Through Protein-Protein Interaction (PPI) network analysis, Support Vector Machine-Recursive Feature Elimination (SVM-RFE) , and Extreme Gradient Boosting (XGBoost) machine learning, we identified Cytochrome P4501B1 (CYP1B1) and Electron Transfer Flavoprotein Alpha (ETFA) as key hub genes. Subsequently, we employed CIBERSORT and single-sample gene set enrichment analysis (ssGSEA) to further investigate the association between hub genes and peripheral immune activation and inflammatory response. Additionally, gene interaction, Drug-mRNA, Transcription Factor (TF)-mRNA, and competing endogenous RNA (ceRNA) networks centered on these hub genes were constructed to explore regulatory mechanisms and potential drug interactions. Finally, validation through bioinformatics and animal experiments identified CYP1B1 as a promising biomarker associated with both PD and insomnia.

Chronic tinnitus is a central nervous system disorder. Currently, the effects of gut microbiota on tinnitus remain unexplored. To explore the connection between gut microbiota and tinnitus, we conducted 16S rRNA sequencing of fecal microbiota and serum metabolomic analysis in a cohort of 70 patients with tinnitus and 30 healthy volunteers. We used the weighted gene co-expression network method to analyze the relationship between the gut microbiota and the serum metabolites. The random forest technique was utilized to select metabolites and gut taxa to construct predictive models. A pronounced gut dysbiosis in the tinnitus group, characterized by reduced bacterial diversity, an increased Firmicutes/Bacteroidetes ratio, and some opportunistic bacteria including Aeromonas and Acinetobacter were enriched. In contrast, some beneficial gut probiotics decreased, including Lactobacillales and Lactobacillaceae. In serum metabolomic analysis, serum metabolic disturbances in tinnitus patients and these differential metabolites were enriched in pathways of neuroinflammation, neurotransmitter activity, and synaptic function. The predictive models exhibited great diagnostic performance, achieving 0.94 (95% CI: 0.85-0.98) and 0.96 (95% CI: 0.86-0.99) in the test set. Our study suggests that changes in gut microbiota could potentially influence the occurrence and chronicity of tinnitus, and exert regulatory effects through changes in serum metabolites. Overall, this research provides new perceptions into the potential role of gut microbiota and serum metabolite in the pathogenesis of tinnitus, and proposes the "gut-brain-ear" concept as a pathomechanism underlying tinnitus, with significant clinical diagnostic implications and therapeutic potential.IMPORTANCETinnitus affects millions of people worldwide. Severe cases may lead to sleep disorders, anxiety, and depression, subsequently impacting patients' lives and increasing societal healthcare expenditures. However, tinnitus mechanisms are poorly understood, and effective therapeutic interventions are currently lacking. We discovered the gut microbiota and serum metabolomics changes in patients with tinnitus, and provided the potential pathological mechanisms of dysregulated gut flora in chronic tinnitus. We proposed the innovative concept of the "gut-brain-ear axis," which underscores the exploration of gut microbiota impact on susceptibility to chronic tinnitus through serum metabolic profile modulation. We also reveal novel biomarkers associated with chronic tinnitus, offering a new conceptual framework for further investigations into the susceptibility of patients, potential treatment targets for tinnitus, and assessing patient prognosis. Subsequently, gut microbiota and serum metabolites can be used as molecular markers to assess the susceptibility and prognosis of tinnitus.Furthermore, fecal transplantation may be used to treat tinnitus.